The 64-year-old star has responded after the White House criticised his acting abilities following a talk where he accused US President Donald Trump of war crimes.
In a statement to The Hollywood Reporter, Clooney said: "Families are losing their loved ones. Children have been incinerated. The world's economy is on a knife's edge.
"This is a time for vigorous debate at the highest levels. Not for infantile name-calling.
"I'll start. A war crime is alleged 'when there is intent to physically destroy a nation', as defined by the Genocide Convention and the Rome Statute.
"What is the administration's defence? (besides calling me a failed actor which I happily agree with having starred in Batman and Robin?).
Trump wrote on Truth Social on Tuesday that a "whole civilisation will die tonight, never to be brought back again" if Iran did not agree to terms for a ceasefire.
A conditional two-week ceasefire has since been reached.
On Wednesday, Clooney spoke to 3000 high school students at a Clooney Foundation For Justice event in Cuneo, Italy, and addressed the Middle East situation.
"Some say Donald Trump is fine. But if anyone says he wants to end a civilisation, that's a war crime ...
"You can still support the conservative point of view, but there must be a line of decency, and we must not cross it."
His comments drew the ire of Trump's White House, and communications director Steven Cheung fired back at the actor, posting on X: "The only person committing war crimes is George Clooney for his awful movies and terrible acting ability."
It's not the first time Clooney and Trump have been at odds, as the US President previously mocked him and his wife Amal for obtaining French citizenship.
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